Non-heme iron containing oxygenases have been shown to be involved in a large number of metabolic processes in both mammalian and bacterial systems. The goal of this proposed research program is to analyze the involvement of the non-heme iron in the catalytic pathway of a selected oxygenase. Particular attention will be paid to the possibility of changes in coordination geometry during catalysis, to the relationship between the substrate binding site and the metal ion, to the factors which influence substrate binding and to the possible role of protein functional groups in catalysis. Of particular significance, fluorine containing substrate analogs will be evaluated as specific and effective oxygenase inhibitors which react only after they have been activated by the enzyme at the active site. If this approach is successful, similar compounds should find use as specific oxygenase inhibitors for in vivo use in the clinical treatment of diseases, or in the inhibition of the carcinogenic or mutagenic activity of exogeneous substances.